A cell membrane is a biomembrane that separates the inside and the outside of a cell. Many membrane proteins having a function of providing cellular information or a function of transporting a substance inside and outside the cell are present on the surface of the cell membrane. In recent years, it has been found that membrane proteins are playing important roles in immunity, and that membrane proteins on the cell surface are targeted in antigen-antibody reactions. A concept is therefore proposed that a specific antigen should be fused with a membrane protein and displayed on the surface of a microbial cell to be used as an oral vaccine to artificially induce an antigen-antibody reaction. At present, however, no example of such use has been reported in practice, and only a few examples of application have been described in research papers. For example, an enzyme protein, such as poly-γ-glutamic acid synthetase, is displayed on the cell surface of a host microorganism utilizing a vector including a gene coding for a membrane-binding site (Patent Document 1). However, only lactic bacteria, yeast, and Escherichia coli have been reported as hosts.
Microorganisms belonging to the genus Bifidobacterium (these bacteria are collectively referred to as “bifidobacteria”) are indigenous bacteria that are present in the lower part of the small intestine or in the large intestine of humans and other animals. As bifidobacteria are obligate anaerobic Gram-positive bacteria, bifidobacteria grow in highly selective culture media (aerobic bacteria do not grow), have high affinity for organisms (predominant in the intestines of infants and also abundant in the intestines of adults), and do not have endotoxins unlike Gram-negative bacteria (highly safe). Accordingly, bifidobacteria are generally recognized as safe (GRAS). As some reports show that Bifidobacterium longum binds to mucus comprising mucins, which covers the intestinal tract, bifidobacteria are thought to be more adhesive to the intestinal wall than other bacteria in the intestines.
Although bifidobacteria attract much attention as described above, expression systems for displaying proteins on the cell surface of bifidobacteria have not yet been developed.